NOSTRA-Feasibility Study: A Study Looking at Ultrasound Guided Biopsies for Breast Cancer

Breast Cancer Clinical Trial

— NOSTRA  

Official title:

Can Patients With Residual Cancer After Chemotherapy for Early Breast Cancer be Identified With Multiple Ultrasound-guided Biopsies?

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04118192
• Other study ID #: RG_16-108
• Status: Active, not recruiting
• Start date: May 22, 2019
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: University of Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

A prospective non-randomised multi-centre feasibility study to assess if patients with residual cancer following dual-targeted neoadjuvant chemotherapy treatment for HER2-positive, ER-negative early breast cancer can be identified by multiple ultrasound (US)-guided tumour bed core biopsies

Description:

The NOSTRA-Feasibility study is designed to determine if it is safe to omit surgery after the planned neoadjuvant chemotherapy plus dual-targeted anti-HER2 treatment. The study is needed to determine whether patients with residual cancer can be identified by histological examination of multiple ultrasound-guided tumour bed core biopsies following dual-targeted neoadjuvant treatment for HER2-positive, ER-negative early primary breast cancer and whether there is concordance between local pathology reporting and central pathology reporting by the trials expert pathologists.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with histological diagnosis of operable HER2-positive, ER-negative, early stage invasive breast cancer

• Tumour size = 1cm and visible on US (T1c to T4d)

• Patient fit and willing to receive, or is already receiving and has received no more than five cycles of a NOSTRA-Feasibility Study approved treatment regimen, in the opinion of the responsible clinician

• Eastern Co-operative Group (ECOG) performance status of 0 or 1

• Women of child-bearing potential, prepared to adopt highly effective contraceptive measures if sexually active for at least 6 months after completion of study medication

• Female, 18 years or older

• Able to provide informed consent for the study

• Availability of embedded paraffin tumour blocks from pre-chemotherapy biopsy

• The radiology team are able and willing to perform the tumour bed core biopsies

Exclusion Criteria:

• Previous ipsilateral invasive breast cancer or Ductal Carcinoma in Situ (DCIS)

• Unequivocal evidence of distant metastatic disease at registration

• Multi-focal disease at diagnosis

• Active malignancy

• Previous chemotherapy

• Prior extensive radiotherapy (as judged by the Investigator) to bone marrow

• Risk factors precluding the safe administration of the intended cytotoxic chemotherapy regimen

• Patient unsuitable for the planned dual-targeted anti-HER2 treatment in opinion of the Investigator

• Prior diagnosis of cardiac failure

• Uncontrolled hypertension, coronary heart disease or other significant cardiac abnormality

• Bleeding diathesis

• Any evidence of other disease which in the opinion of the Investigator places the patient at high risk of treatment related complications

• Pregnant (female patients of child bearing potential must have a urine or blood Human Chorionic Gonadotropin test performed to rule out pregnancy prior to study entry)

• Patient lactating

• Patients who have received live vaccine within 4 weeks of the date of study entry

• Any concomitant medical or psychiatric problems which in the opinion of the Investigator would prevent completion of treatment or follow-up

• Patient unfit and/or unwilling to undergo surgery

• Patient unwilling or unable to comply with scheduled visits, treatment plan and study procedures

• Patient has started protocol non-compliant neo-adjuvant chemotherapy

• Patient has started approved neoadjuvant chemotherapy but insufficient data is available to complete relevant CRFs

• Patient has already received more than five cycles of approved neoadjuvant chemotherapy

Additional Inclusion Criteria for ctDNA Sub-Study

• Patient has not yet started neoadjuvant treatment

• Patient is willing and able to give blood samples as per ctDNA Sub-Study Guidelines

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Procedure:
• Tumour bed core biopsy
Collection of up to 8 core biopsies across 4 zones of the whole tumour bed to detect residual cancer post neo-adjuvant treatment

Locations

Country	Name	City	State
United Kingdom	Basildon Hospital	Basildon	Essex
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	City Hospital	Birmingham
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Blackpool Teaching Hospitals NHS Trust	Blackpool
United Kingdom	Southmead Hospital	Bristol
United Kingdom	University Hospital of Llandough	Cardiff
United Kingdom	Cheltenham General Hospital	Cheltenham
United Kingdom	Dumfries and Galloway Royal Infirmary	Dumfries
United Kingdom	Western General	Edinburgh
United Kingdom	Northwick Park Hospital	Harrow
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Royal Liverpool Hospital	Liverpool
United Kingdom	Royal Marsden Hospital	London
United Kingdom	Borders General Hospital	Melrose
United Kingdom	Royal Victoria Infirmary	Newcastle Upon Tyne
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Peterborough City Hospital	Peterborough
United Kingdom	Poole Hospital	Poole
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Singleton Hospital	Swansea
United Kingdom	Arrowe Park Hospital	Upton
United Kingdom	Thomas Linacre Centre	Wigan

Sponsors (3)

Lead Sponsor	Collaborator
University of Birmingham	Cancer Research UK, Roche Pharma AG

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Observed number of patients with false negative biopsies	The observed number of patients with false negative biopsies (i.e. no tumour in the biopsy but tumour in the surgical specimen) as a proportion of all those assessed by Local Histopathology Review	12 months post last patient recruited
Secondary	Concordance between Local and Central Histopathology Review of core biopsies	is defined as the number of patients whose initial local pathological assessment of pCR is confirmed by Central Histopathology Review	12 months post last patient recruited
Secondary	Compliance with treatment	assessed by calculating relative dose intensity taking into account of both reductions in dose and delays to treatment.	12 months post last patient recruited
Secondary	Time to local recurrence	Compliance with neoadjuvant and adjuvant treatment; will be assessed by calculating relative dose intensity taking into account of both reductions in dose and delays to treatment.	Number of days from registration to local recurrence (if within trial duration, approximately 6.5 years)
Secondary	Time to distant recurrence	defined in whole days from date of registration to distant recurrence or death from any cause. Patients who are alive and without distant recurrence at the time of analysis will be censored at the date last seen.	Number of days from registration to local recurrence (if within trial duration, approximately 6.5 years)
Secondary	Overall survival	defined in whole days as the date of registration to death from any cause. Patients alive at the time of analysis will be censored at the date last seen.	Whole days from registration to death from any cause (if within trial duration, approximately 6.5 years)
Secondary	Re-evaluation of the primary outcome using the central pathological review determination of RCB to define false negative biopsies as RCB-0 or 1 (i.e. no tumour or minimal residual disease) in the core biopsies but RCB-2 or 3 in the surgical specimen	This will be reported as a proportion of all recruited patients	Post-last patient last surgery (within approximately 6.5 years of start of trial)
Secondary	Ability of the axillary lymph node assessments post-neoadjuvant treatment to identify definitive axillary lymph node involvement determined by surgery histopathology	Sensitivity, specificity and false negative rates will be reported.	Post-last patient last surgery (within approximately 6.5 years of start of trial)